We have previously postulated that the hepatic necrosis caused by isoniazid and iproniazid results from the liberation and subsequent metabolic activation of their hydrazino moieties to acylating and alkylating intermediates in the body (ZO1 HL 00877-02 LCP, ZO1 HL 00878- 01 LCP, ZO1 HL 00879-01 LCP). We now compare the rates of metabolism of hydrazino compounds by the proposed toxic pathways in rats, and the extent of hepatic necrosis and covalent binding.